The goal of this Visiting Scientist Proposal is to incorporate molecular biology into current studies on the immune response to insulin in man. T cell clones derived from both Type I and Type II diabetics will be examined at the genomic level, and the amino acid composition their antigen receptors will be determined from cDNA clones. These T cells recognize epitopes on human and animal insulin in association with Class II HLA antigens. The project is designed to provide Dr. Thomas, as a Visiting Researcher, with the skills required for Southern and Northern gel analyses, preparation of cDNA clones, and DNA sequencing. New and important information will be obtained on the diversity of T cell receptor structures responsible for insulin immunity. T cell V-region gene probes obtained from insulin treated diabetics will be used to determine if similar TcR gene products are part of the autoimmune prodrome of Type I diabetes. The skills acquired from this project will provide Dr. Thomas's laboratory with important techniques that will further our understanding of Type I diabetes and other autoimmune endocrine disorders.